After a period of cardiac arrest, external compression partially reestablishes cerebral blood flow (CBF) until full restoration of circulation can be achieved by cardioversion. Depending on the level of CBF attained during cardiopulmonary resuscitation (CPR), partial cerebral ischemia may continue and thereby prolong the insult to the brain. The overall aim of this project is to investigate the physiological consequences of CPR on the brain, and then based on this knowledge, design new strategies that can be utilized during CPR to enhance cerebral recovery. The mechanics, physiology and pharmacology of CPR and cerebral ischemia have not been well studied in the infant. We will conduct investigations both in an infant model utilizing two-week old pigs and in an adult model utilizing dogs. CPR efforts in children are often prolonged. In infant piglets, CBF and metabolism could not be sustained as long as in adult dogs. We will delineate the mechanism of this failure in infant pigs and employ innovative CPR techniques to prolong adequate cerebral perfusion. The effects of pharmacological and mechanical interventions made during CPR on recovery of regional CBF, global cerebral metabolism, somatosensory and brainstem auditory evoked potentials, electroencephalogram and in some cases, neurological function will be evaluated. We will determine if equipotent pressor doses of different classes of adrenergic drugs given during CPR have different effects on the recovery of cerebral metabolism, regional CBF and electrical function. We will find out if the blood-brain barrier is disrupted during CPR or during the cerebral hyperemia that follows cardioversion. Alternatively, we will show if circulating epinephrine gains access to the brain by saturating the enzymatic barrier for catecholamines. Reperfusion injury associated with oxygen-derived free radical production may commence with initiation of CPR prior to cardiac resuscitation. We will establish whether modest levels of cerebral reoxygenation achieved with CPR generates superoxide anion on the cortical surface, and contrast this with full reperfusion after cardiac resuscitation. We will determine how free radical scavengers can best be administered during CPR to inhibit cortical superoxide appearance. Then we will see if administration of these agents during CPR improves recovery of brain electrical function and metabolism, blunts postischemic reductions of CBF, and enhances neurological outcome. These studies may have a significant impact on the practice of CPR.